DESCRIPTION: (Verbatim) - Excessive exposure to solar radiation results in erythema (sunburn) and has been linked to premature skin aging, immunosuppression and skin cancer. Despite greater awareness by the public of the harmful effects of exposure to sunlight and increased use of sunscreens, skin cancer rates have continued to rise. Currently accepted test methods for determining skin protection factors (SPF) of ultraviolet-B (UVB) sunscreens involve measuring increased UVB irradiation needed to cause erythema in human panelists. However, this test method is sub-optimal because of possible risk to human panelists and because the relationship between erythema and skin cancer is unclear. No method is currently accepted for determining protection provided against UVA irradiation, which is also believed to present skin cancer risks. The goal of the present proposal is to develop methodology which overcomes the drawbacks of current sunscreen testing. A mechanistic assay utilizing a highly differentiated skin model and endpoints which directly measure genotoxicity will be used. DNA strand breaks, thymine dimer photoproducts, 8-hydroxyguanosine and p53 protein expression will be determined by various convenient methods. These methods measure events directly related to skin cancer and will give producers and regulators of sunscreens important new tools for assessing the true efficacy of sunscreen formulations. Phase I research will develop methods for determining a sunscreens "DNA protection factor" - the ultimate goal of Phase II research will be to submit results of multi-lab, GLP studies to the FDA for approval as a validated method. PROPOSED COMMERCIAL APPLICATION: The proposed methods for determining genotoxicity in in vitro human skin models will find application in product safety assessment for a broad variety of pharmaceutical, chemical, and consumer product companies. Companies which produce over the counter sunscreen drug products, or other pharmaceutical, cosmetic or household consumer products which may come in contact with skin or are intended for topical use will utilize this technology.